Mutational Signatures Of DDT: The Role Of A Controversial Persistent Endocrine Disrupting Pollutant On Prostate Cancer Aetiology
Funder
National Health and Medical Research Council
Funding Amount
$991,000.00
Summary
No carcinogen or prevention has been identified for prostate cancer (PCa). As carcinogens are commonly mutagens, we will use genomic interrogation to determine if extensive use of the hormone-disrupting pesticide DDT during the 40's to late 80's increased PCa globally. Having access to prostate tumours from men with biochemically confirmed lifelong DDT-exposure, will provide a measurable genomic signature to evaluate the impact of DDT globally, including Australia.
Understanding Tumour Plasticity And The Microenvironment Using Single-cell Technologies To Identify Novel Targets For Metastatic Castration-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$653,578.00
Summary
Most prostate cancer patients respond well to treatment, but some develop metastatic disease and respond poorly. During metastasis the cancer spreads to multiple organs and new combinations of genes become activated, making it difficult to develop new treatments. We will investigate these patterns of activation of genes in metastatic samples and how the immune system interacts with the cancer. We will use computational models to identify new drug targets and evaluate immunotherapy as an option.
Engineering CYP17A1 Inhibitors For Castrate-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$519,428.00
Summary
As prostate cancer progresses it becomes resistant to first line treatments and the current second line treatments have untoward side effects. This proposal will provide proof of principal for new selective drugs to be developed. We propose an innovative strategy to develop new selective drugs for the treatment of prostate cancer. This new therapeutic approach will identify new compounds for patients specifically with castrate sensitive and resistant prostate cancer.
An Integrative Approach To Define And Attenuate Genomic Risk Of Coronary Artery Disease
Funder
National Health and Medical Research Council
Funding Amount
$988,454.00
Summary
One in four individuals that have a heart attack do not have traditional risk factors such as high blood cholesterol levels. This highlights the importance of 'family history', which we can now quantify as 'genetic risk'. These studies will determine (i) which genes are important in contributing to this genetic risk (ii) how these genes change biological pathways to increase risk and (iii) the effectiveness of modulating these biological pathways to reduce the risk of heart disease.
HTLV-1 is a lifelong infection of immune cells that sustains high infection rates up to 45% in key Australian communities. Despite HTLV-1 causing serious malignancy and inflammatory co-morbidities that shorten lifespan, few biomedical interventions are available. We will examine how the virus grows and alters immune responses to cause disease. With this, we can develop antiviral treatments to reduce virus infected cells, and make new diagnostic biomarker assays suitable for remote settings.
Structure And Biophysical Analysis Aided Design Of Novel Toxoid Vaccines For A Major Class Of Bacterial Toxins.
Funder
National Health and Medical Research Council
Funding Amount
$608,425.00
Summary
Inactivated bacterial toxins (toxoids), such as the tetanus vaccine, are safe and effective vaccines. Cholesterol dependent cytolysins (CDCs) are bacterial toxins produced by many important human pathogens including Group A Streptococcus (GAS) and Pneumococcus. GAS has no available vaccine and Pneumococcus does not have a universal vaccine. We have developed a new way of inactivating CDCs based on new knowledge of how they target human cells and will use this knowledge to make new vaccines.
Targeting The Crosstalk Between Metabolism And Epigenetics To Treat Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,032,259.00
Summary
Virtually all liver disease related morbidity and mortality is a consequence of fibrosis that culminates in liver failure or liver cancer. Since anti-fibrotic drugs are not available, new approaches to drug development are required. We have discovered a novel strategy for such drug development by modifying the expression of a specific gene (RARRES1) in a highly targeted manner and thereby interrupting the energy production that is needed by cells to drive fibrosis.
Evidence For Action On Cold, Damp And Mould In Australian Homes
Funder
National Health and Medical Research Council
Funding Amount
$955,649.00
Summary
We know that living in cold and damp homes is bad for people's health. Surprisingly in Australia we do not know how much exposure to poor conditions and financial hardship combines to generate poor health at the population level. We will quantify this impact and estimate the benefit of interventions (such as mould removal and assistance for paying utility bills). This project will provide governments with evidence for tackling this housing-related health problem.
The Future In Our Hands: Screening For Preclinical Alzheimer's Disease By Analysing Hand Movements
Funder
National Health and Medical Research Council
Funding Amount
$899,782.00
Summary
Alzheimer's disease (AD) starts damaging the brain 10-20 years before memory problems begin. By the time of diagnosis, it is hard to treat because the damage is so severe. We need a way to detect AD much earlier. We will develop a simple new computer test to detect early signs of AD by recording and analysing hand movements. Then people can start prevention earlier and scientists can research better treatments to improve people's quality of life and reduce the number of people with dementia.
Hysterectomy, Oophorectomy And Long-term Chronic Disease - The HOLD Study
Funder
National Health and Medical Research Council
Funding Amount
$690,006.00
Summary
Hysterectomy, with or without the removal of ovaries, undertaken for non-cancerous problems may have long-term consequences for other health conditions like cardiovascular disease and cancer, but existing evidence is inconsistent. This large population-based study will use linked health data from the states and the Commonwealth to investigate these associations. The information from our study will help women and their doctors to make the better-informed decisions about their treatment.